Inherited Metabolic Disorders

Inherited metabolic disorders are caused by a genetic mutation, creating an enzyme deficiency that leads to an inability to break down metabolic waste products. The result is a progressive cellular accumulation of toxic substances, which damages organs, tissues and the central nervous system. 

If left untreated, these disorders result in a progressive disease with neurological and psychomotor obstruction, skeletal abnormalities, and life-threatening cardiac and pulmonary complications. [1,2] Allogeneic hematopoietic cell transplantation (HCT) can prevent this progressive deterioration by introducing enzyme-producing cells that can cross the blood-brain barrier. [3] 

A study of HCT in 217 patients with Hurler syndrome found that preservation of cognitive function at the time of transplant and younger age at transplantation were major predictors for superior post-transplant cognitive development. [4] 

Allogeneic HCT can treat: 

• Hurler syndrome (MPS I) 
• Hunter syndrome (MPS II) [5] 
• Maroteaux-Lamy syndrome (MPS VI) 
• Sly syndrome (MPS VII) 
• Cerebral X-linked adrenoleukodystrophy 
• Globoid-cell leukodystrophy (Krabbe disease) 
• Metachromatic leukodystrophy 
• Gaucher disease 
• Fucosidosis 
• Alpha-mannosidosis 
• Aspartylglycosaminuria 
• Mucolipidosis II (I-cell disease) 
• Wolman syndrome 

Outcomes 

Data in this section have been prepared by the CIBMTR® (Center for International Blood and Marrow Transplant Research®). The CIBMTR is a research collaboration between the National Marrow Donor Program ® (NMDP)/Be The Match® and the Medical College of Wisconsin. 

Figure 1. Pediatric Survival after Allogeneic HCT for Inherited Metabolic Disorders

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HCT Consultation Timing Guidelines 

The National Marrow Donor Program® (NMDP)/Be The Match® and the American Society for Transplantation and Cellular Therapy (ASTCT) have jointly developed guidelines for transplant consultation and referral timing based on disease characteristics. [6] The National Comprehensive Cancer Network Clinical Practice Guidelines (NCCN Guidelines®) were consulted when developing these guidelines and are a valuable tool in determining risk stratification. [7] 

Our guidelines highlight disease categories that include patients at risk for disease progression and who should be referred for a consultation for transplantation. [6]

Transplant Consultation Guidelines: Inherited Metabolic Disorders 

Including Hurler syndrome, adrenoleukodystrophy and others 

• At diagnosis or if detected on newborn screening 

Download as slides  

View complete HCT Consultation Timing Guidelines

Clinical Trials Search and Support

The NMDP/Be The Match offers the Be The Match® Jason Carter Clinical Trials Search and Support (CTSS) program, which can provide clinical trial navigation to your patients. The CTSS Program was created to help people with blood cancers or blood disorders and their families find and join clinical trials.

For more information, visit Clinical Trials Search and Support.  

References  

1. Domen J, Gandy K, Dalal J. Emerging uses for pediatric hematopoietic stem cells. Pediatr Res. 2012; 71(4-2): 411-417. Access
2. Boelens JJ, Orchard PJ, Wynn RF. Transplantation in inborn errors of metabolism: current considerations and future perspectives. Brit J Haematol. 2014; 167(3): 293-303. Access
3. Prasad VK, Kurtzberg J. Transplant outcomes in mucopolysaccharidoses. Sem Hematol. 2010; 47(1): 59-69. Access
4. Aldenhoven M, Wynn RF, Orchard PJ, et al. Long-term outcome of Hurler syndrome patients after hematopoietic cell transplantation: an international multicenter study. Blood. 2015; 125(13): 2164-2172. Access
5. Kubaski F, Yabe H, Suzuki Y, et al. Hematopoietic stem cell transplantation for patients with mucopolysaccharidosis II. Biol Blood Marrow Transplant. 2017; 23(10): 1795-1803. Access
6. NMDP/Be The Match and ASTCT Recommended Timing for Transplant Consultation. Download (PDF)
7. National Comprehensive Cancer Network. NCCN Guidelines. 2023. Access